We propose a wave seven telephone diagnostic interview follow-up of the MOAFTS (Missouri Adolescent Female Twin Study) young cohorts A and B (target N=2100 twin interviews), and for some participants who have not yet provided samples, saliva sample collection (target N=840) for genotyping for zygosity confirmation. MOAFTS is a prospective study of a birth cohort of female like-sex twin pairs (N=370 African- American pairs, N=1999 European/Other Ancestry pairs) identified from birth records and first assessed in adolescence, at median age 16. Goals of the project are to characterize, in a broadly representative general population female twin cohort, gene-environment interplay in alcoholism and associated substance use disorders, focusing on (i) parental alcoholism and its associated twin offspring environmental risk-exposures and outcomes, and (ii) the development and course of female drinking and alcohol-related problems, as well as other substance use and problems (particularly tobacco use and dependence), through adolescence into young adulthood, emphasizing precursors/mediators and moderators of genetic and environmental effects on both onset of and recovery from problems. In the most recent data-collection, interviews were completed with approximately 3500 respondents at ages 21-30. Wave seven will provide a further follow-up of alcohol and other substance use and problems, and proximal environmental exposures, so that most twins are through their period of greatest risk for onset of alcohol problems, and the sample will be old enough to be informative about the predictors of remission versus persistence of alcohol problems and heavy drinking (target N=700 assessed at age 30, N=1400 assessed at age 28/N=100 new dependence cases). Our research is motivated by the concern that the genetic transmission of risks of alcohol and other substance use disorders frequently occurs in the context of high-risk environmental exposures commonly associated with parental alcoholism - including interpersonal conflict and divorce or never-cohabitation, step-parent presence, childhood assaultive trauma, family socioeconomic disadvantage - risks that need not be reduced by the departure of an alcoholic parent from the home. Through completion of the wave seven data-collection and data-analyses, our goals are to understand how these early environmental exposures, in combination with genetic effects, influence onset and course of heavy drinking and alcohol problems, either directly, or through effects on timing of onset of alcohol use and on comorbid substance use, and effects on subsequent adult role changes of the twins (early or delayed parenting;relationship formation, conflict and dissolution;education completion, employment, and adult peer relationships);and to identify other variables (history of childhood or adolescent-onset psychopathology, other substance use disorders) that may mediate or moderate these relationships. Current understanding of the genetic epidemiology of female alcohol use disorders is based largely on either retrospective or underpowered studies - a gap that the MOAFTS cohort will help to fill. PUBLIC HEALTH RELEVANCE: Alcohol misuse by young women is associated with significant impairments including difficulties in forming and maintaining stable romantic relationships, delayed reproduction, and impaired parenting, as well as risks associated with hazardous use. Better understanding of risk-mechanisms leading to the onset and persistence versus remission of female alcohol misuse in adolescence and young adulthood will have important implications for motivating and better targeting prevention and intervention efforts for young women and, in some cases, mitigating risks to their children.